Participation of voltage-gated sodium and calcium channels in the acute cardiac effects of toluene.

Inhaling solvents can lead to occurrence of cardiac arrhythmias and sudden sniffing death. Mechanisms related to this phenomenon are not fully understood. The purpose of this study was to investigate the effect of acute toluene exposure on heart reactivity to epinephrine and the participation of voltage-gated sodium and calcium channels. We found that acute toluene exposure increased perfusion pressure, left ventricular developed pressure, and heart rate. These actions were inhibited by lidocaine and nifedipine. Our results suggest that acute toluene exposure modify voltage-gated sodium and calcium channel function and expression likely due to a cardiac adrenergic mechanism and these effects could be participating, at least in part, in the presence of cardiac arrhythmias. To our best knowledge, this is the first report to establish a direct participation of voltage-gated Na+ and Ca2+ channels, toluene and epinephrine on cardiac function in rats.

Impacts of standard wine-making process on the survival of Lobesia botrana larvae (Lepidoptera: Tortricidae) in infested grape clusters.

To determine the risk winery waste poses for the spread of Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) in California, we evaluated the survival of larvae in artificially infested grape clusters (Vitis vinifera L.) processed for wine making. The trial consisted of five treatments: whole cluster pressing to 1 bar (100,000 Pa); whole cluster pressing to 2 bars (200,000 Pa); destemming and berry pressing to 1 bar; destemming and berry pressing to 2 bars; and control. Each treatment was replicated with the following five winegrape varieties: Chardonnay, Sauvignon Blanc, Gewürztraminer, Yellow Muscat, and Cabernet Sauvignon. All winery waste was inspected for larval survival. No live larvae were recovered from any of the treatments in all five varieties; therefore, the hypothesis that green winery waste contributes to the spread of L. botrana was rejected.

End of life, death and dying in neonatal intensive care units in Latin America.

AIM: Most analyses of end of life decisions in Neonatal Intensive Care Units (NICUs) have come from Europe/English-speaking countries. Would decisions be different in Latin American NICUs? Therefore, we aim to evaluate the approach to dying infants/families in NICUs in Latin America. METHODS: Multinational descriptive study of all deaths in babies born at >22 weeks in eight NICUs in five Latin American countries. Deaths were categorized as: (i) no Cardiopulmonary Resuscitation (CPR) or life support offered; (ii) life support initiated but do not resuscitate (DNR) orders written or no CPR provided; (iii) full life support and CPR; and (iv) unclassifiable. RESULTS: There were 100 deaths, 81% in >27 weeks. Seventeen infants received no CPR/life support at birth, 10 died in DR and seven in NICU. There were 27 infants in group 2, 54 in group three and two in group 4. No baby had care withdrawn or care withdrawn/CPR withheld. Thirty-two infants had 'do not resuscitate' order. Decisions without parents' involvement in 15%, both parents present at death 24% and sedatives/narcotics documented 14%. CONCLUSIONS: Latin American NICUs differ from those in Northern Europe/English-speaking countries. More deaths are accompanied by full life support and CPR. DNR orders are rare. Withdrawal of life support is virtually non-existent. Latin American's doctors are more likely to make decisions without the objections of family about withholding life-sustaining treatment.

Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain.

OBJECTIVE: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline. METHODS: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged ≥ 18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed. RESULTS: We identified 21,851 patients with HF (age 78.0 ± 11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9 ± 72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population. CONCLUSIONS: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF.

Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system. / Uveítis intermedia como presentación inicial de un linfoma primario del sistema nervioso central.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

Acute Intermittent Porphyria in a Man with Dual Enzyme Deficiencies.

Porphyrias are a heterogeneous group of metabolic disorders that result from the altered activity of specific enzymes of the heme biosynthetic pathway and are characterized by accumulation of pathway intermediates. Porphyria cutanea tarda (PCT) is the most common porphyria and is due to deficient activity of uroporphyrinogen decarboxylase (UROD). Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias, caused by decreased activity of hydroxymethylbilane synthase (HMBS). An Argentinean man with a family history of PCT who carried the UROD variant c.10_11insA suffered severe abdominal pain. Biochemical testing was consistent with AIP, and molecular analysis of HMBS revealed a de novo variant: c.344 + 2_ + 5delTAAG. This is one of the few cases of porphyria identified with both UROD and HMBS mutations and the first confirmed case of porphyria with dual enzyme deficiencies in Argentina.

Empowering knowledge generation through international data network: the IMeCCHI-DATANETWORK.

INTRODUCTION: The International Methodology Consortium for Coded Health Information (IMeCCHI) is a collaboration of health services researchers who promote methodological advances in coded health information. The IMeCCHI-DATANETWORK initiative focuses on developing a multi-purpose distributed data infrastructure and common data model (CDM) to enable cross-border data sharing and international comparisons. METHODS: IMeCCHI consortium partners from six different countries - Canada, Denmark, Italy, New Zealand, South Korea, and Switzerland - used a questionnaire to describe their original databases which differ in size, structure, content and coding systems. To standardize these data, they agreed on a CDM and mapped their population-based databases to meet the CDM specifications. At the end of this process, local data had a more homogenous content and structure, which made them syntactically and semantically interoperable. Data transformation was performed using a common data management software called TheMatrix. RESULTS: The CDM encompasses four tables of structured data (person characteristics, hospitalizations, outpatient prescription medication and death), linked at the individual level through a person identifier. It can be used to answer research questions across countries using locally converted databases, which facilitates study replication in a distributed fashion. As a proof-of-concept study, an initial research question was addressed using an agreed protocol. Local data were transformed in csv files in the CDM structure and TheMatrix was tested to transform the standardized data from each partner into local analytical datasets. This allowed results to be shared between countries, whilst maintaining local control over each region's data. CONCLUSION: The IMeCCHI-DATANETWORK, a model of a distributed data network, demonstrated that it is feasible to analyze international data using standardized analytical methods that enable independent analyses by regions, without relocating datasets thereby protecting local confidentiality obligations. The distributed data infrastructure can produce results that can be generalized to several countries, while facilitating cross-border data sharing and international comparisons. KEYWORDS: Common data model, international comparison, cross-border data sharing, interoperability, observational data.

Developing a Data Integrated COVID-19 Tracking System for Decision-Making and Public Use.

INTRODUCTION: The unprecedented COVID-19 pandemic unveiled a strong need for advanced and informative surveillance tools. The Centre for Health Informatics (CHI) at the University of Calgary took action to develop a surveillance dashboard, which would facilitate the education of the public, and answer critical questions posed by local and national government. OBJECTIVES: The objective of this study was to create an interactive method of surveillance, or a "COVID-19 Tracker" for Canadian use. The Tracker offers user-friendly graphics characterizing various aspects of the current pandemic (e.g. case count, testing, hospitalizations, and policy interventions). METHODS: Six publicly available data sources were used, and were selected based on the frequency of updates, accuracy and types of data, and data presentation. The datasets have different levels of granularity for different provinces, which limits the information that we are able to show. Additionally, some datasets have missing entries, for which the "last observation carried forward" method was used. The website was created and hosted online, with a backend server, which is updated on a daily basis. The Tracker development followed an iterative process, as new figures were added to meet the changing needs of policy-makers. RESULTS: The resulting Tracker is a dashboard that visualizes real-time data, along with policy interventions from various countries, via user-friendly graphs with a hover option that reveals detailed information. The interactive features allow the user to customize the figures by jurisdiction, country/region, and the type of data shown. Data is displayed at the national and provincial level, as well as by health regions. CONCLUSION: The COVID-19 Tracker offers real-time, detailed, and interactive visualizations that have the potential to shape crucial decision-making and inform Albertans and Canadians of the current pandemic.

Pseudolattice theory of the surface tension of ionic liquid-water mixtures.

A theoretical model for ionic liquids (ILs) based on a pseudoreticular structural model for the bulk mixture is reported. The original Bahe-Varela pseudolattice theory of concentrated ionic solutions is modified and the short-range interactions modeled by a Lennard-Jones potential. In this framework, the surface tension of the pure IL is calculated and the correct dependence of this magnitude on the density of the liquid, as provided by the parachor, is recovered. The anions in the mixture are assumed to form a continuum structureless neutralizing background, and that the organic cations and water molecules are placed in the nodes of the pseudolattice. The surface pressure of IL-water mixtures is calculated using a localized model for the adsorption of particles in the surface of the mixture and a mean-field Bragg-Williams approximation for the chemical potential of the adsorbed particles in the pseudolattice. The theoretical predictions are tested with experimental data of several ionic liquid aqueous mixtures.

Nonequilibrium nanothermodynamics.

Entropy production for a system outside the thermodynamic limit is formulated using Hill's nanothermodynamics, in which a macroscopic ensemble of such systems is considered. The external influence of the environment on the average nanosystem is connected to irreversible work with an explicit formula based on the Jarzynski equality. The entropy production retains its usual form as a sum of products of fluxes and forces and Onsager's symmetry principle is proven to hold for the average nanosystem, if it is assumed to be valid for the macroscopic ensemble, by two methods. The first one provides expressions that relate the coefficients of the two systems. The second gives a general condition for a system under an external force to preserve Onsager's symmetry.

Orexin expression is regulated by alpha-melanocyte-stimulating hormone.

The hypothalamic melanocortin system plays a fundamental role in the regulation of energy homeostasis. Orexins (hypocretins) are also involved in a diverse range of physiological processes, including food intake. Previous evidence has suggested that hypothalamic orexin expression may be influenced by the central melanocortin system. Here, we studied orexin mRNA levels in pro-opiomelanocortin-deficient (Pomc(-/-)) mice, a mouse model lacking all endogenously produced melanocortin peptides. Orexin expression in the lateral hypothalamus was significantly increased in corticosterone deficient Pomc(-/-) mice. Furthermore, when circulating glucocorticoids were restored to levels within the physiological range, orexin expression remained elevated. However, i.c.v. administration of the melanocortin alpha-melanocyte-stimulating hormone (MSH) to Pomc(-/-) mice reduced orexin expression back down to wild-type levels. This was independent of the effects of alpha-MSH on food intake because elevated orexin expression persisted in Pomc(-/-) mice pairfed to alpha-MSH-treated animals. These data indicate that alpha-MSH may play a role in the regulation of orexin expression in Pomc(-/-), with an elevation in orexin levels contributing to the hyperphagia seen in these animals.

In vitro evaluation of an axial flow pump: mock-pump interaction and an approach to control.

Continuous flow pump support has emerged as an alternative therapy in patients with congestive heart failure. For long-term applications, it is important to have a control system that changes the pump function according to the physiological conditions of the patient, thereby preventing risk situations. In the early stages of development, the evaluation of control algorithms for artificial blood pumps can be done in vitro using cardiovascular mock systems. A systemic cardiovascular mock loop was constructed and an axial flow pump was connected to it. The level of pump assistance was estimated using a pulsatility index (IPAo) obtained from the aortic pressure wave. An IPAo proportional-integral control system was implemented and its responses to peripheral resistance and systemic compliance changes were evaluated. IPAo is an indicator of the assistance level of a continuous flow pump operated at constant speed. The IPAo control algorithm responds by increasing the pump speed when peripheral resistance or systemic compliance is reduced. Control system operation around an IPAo fixed value provides a safety point for pump operation by maintaining aortic pressure pulsatility and avoiding ventricular suction. In vitro experimental results show that the IPAo can be taken into consideration in multiobjective control algorithm designs.

Características clínicas, manejo y riesgo de complicaciones a un año en pacientes con insuficiencia cardíaca con y sin diabetes tipo 2 en España / Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain

Objetivos: Describir las características clínicas y el manejo terapéutico y determinar los eventos cardiovasculares tras un año de seguimiento en una población contemporánea con insuficiencia cardíaca (IC) con y sin diabetes tipo 2 en España. También se analizó en la población DAPA-HF (pacientes que cumplieron la mayoría de los criterios de inclusión del estudio DAPA-HF) y en los pacientes tratados basalmente con inhibidores SGLT2.Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La fecha índice fue 1 de enero de 2019. Se seleccionaron sujetos≥18 años que recibieron tratamiento por IC en 2019. Se analizaron los eventos durante 2019.Resultados: Se identificaron 21.851 pacientes con IC (78±11,3 años; 53% varones; 50,9% IC con fracción de eyección reducida; 44,5% en clase funcional NYHA II). La prevalencia de IC fue del 1,88% y la incidencia 2,83 por 1.000 pacientes-año. El 66,1% tomaba inhibidores del sistema renina-angiotensina, el 69,4% betabloqueantes, el 31,2% antialdosterónicos y el 7,5% sacubitrilo/valsartán. Durante el año de seguimiento, el 29,8% fue hospitalizado por descompensación de la IC (tiempo medio primer evento 120,9±72,5 días), un 12,3% murieron, un 8,1% murieron durante la hospitalización. Los eventos fueron más frecuentes en los pacientes con diabetes tipo 2. Las hospitalizaciones por IC fueron más comunes en la población similar a DAPA-HF.Conclusiones: En España, la población con IC es anciana y tiene muchas comorbilidades. Aproximadamente la mitad de los pacientes tienen IC con fracción de eyección reducida. Existe margen de mejora en el manejo de la IC, en particular mediante el empleo de aquellos fármacos que reducen tanto la hospitalización por IC como la mortalidad, para disminuir la carga de IC (AU)

Objective: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline.Methods: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged≥18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed.Results: We identified 21,851 patients with HF (age 78.0±11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9±72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population.Conclusions: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF (AU)

Sphere to rod transitions in homologous alkylpyridinium salts: a Stauff-Klevens-type equation for the second critical micelle concentration.

In the present paper, we analyze the dependence of the second critical micelle concentration (second cmc) of ionic amphiphiles on the number of atoms in the hydrocarbon molecular chain, n(c). A molecular thermodynamic model for the interaction energy between the end caps of rodlike micelles, g(N), is introduced and the linear dependence of this object on n(c) analyzed, thus leading to a Stauff-Klevens-like behavior of the second cmc. The predictions agree with previously reported data for n-alkyldimethylbenzylammonium chloride (C(n)BACl) for n-alkylpyridinium chloride (C(n)PyCl) and n-alkyltrymethylammonium bromide (C(n)TABr) at 35 degrees C. These conclusions are reinforced by the conductivity, density, and ultrasound velocity measurements of the second cmc of several C(n)PyCl (n=12, 14, 16) and n-alkylpyridinium bromides (C(n)PyBr, n=12, 14, 15, 16) presented in this paper.

Structural and electronic properties of zigzag InP nanoribbons with Stone-Wales type defects.

By means of density-functional-theoretic calculations, we investigate the structural and electronic properties of a hexagonal InP sheet and of hydrogen-passivated zigzag InP nanoribbons (ZInPNRs) with Stone-Wales (SW)-type defects. Our results show that the influence of this kind of defect is not limited to the defected region but it leads to the formation of ripples that extend across the systems, in keeping with the results obtained recently for graphene and silicene sheets. The presence of SW defects in ZInPNRs causes an appreciable broadening of the band gap and transforms the indirect-bandgap perfect ZInPNR into a direct-bandgap semiconductor. An external transverse electric field, regardless of its direction, reduces the gap in both the perfect and defective ZInPNRs.

Effect of Bifidobacterium upon Clostridium difficile Growth and Toxicity When Co-cultured in Different Prebiotic Substrates.

The intestinal overgrowth of Clostridium difficile, often after disturbance of the gut microbiota by antibiotic treatment, leads to C. difficile infection (CDI) which manifestation ranges from mild diarrhea to life-threatening conditions. The increasing CDI incidence, not only in compromised subjects but also in traditionally considered low-risk populations, together with the frequent relapses of the disease, has attracted the interest for prevention/therapeutic options. Among these, probiotics, prebiotics, or synbiotics constitute a promising approach. In this study we determined the potential of selected Bifidobacterium strains for the inhibition of C. difficile growth and toxicity in different carbon sources. We conducted co-cultures of the toxigenic strain C. difficile LMG21717 with four Bifidobacterium strains (Bifidobacterium longum IPLA20022, Bifidobacterium breve IPLA20006, Bifidobacterium bifidum IPLA20015, and Bifidobacterium animalis subsp. lactis Bb12) in the presence of various prebiotic substrates (Inulin, Synergy, and Actilight) or glucose, and compared the results with those obtained for the corresponding mono-cultures. C. difficile and bifidobacteria levels were quantified by qPCR; the pH and the production of short chain fatty acids was also determined. Moreover, supernatants of the cultures were collected to evaluate their toxicity using a recently developed model. Results showed that co-culture with B. longum IPLA20022 and B. breve IPLA20006 in the presence of short-chain fructooligosaccharides, but not of Inulin, as carbon source significantly reduced the growth of the pathogen. With the sole exception of B. animalis Bb12, whose growth was enhanced, the presence of C. difficile did not show major effects upon the growth of the bifidobacteria. In accordance with the growth data, B. longum and B. breve were the strains showing higher reduction in the toxicity of the co-culture supernatants.

Molecular dynamics simulation of the behaviour of water in nano-confined ionic liquid-water mixtures.

This work describes the behaviour of water molecules in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid under nanoconfinement, between graphene sheets. By means of molecular dynamics simulations, the adsorption of water molecules at the graphene surface is studied. A depletion of water molecules in the vicinity of the neutral and negatively charged graphene surfaces, and their adsorption at the positively charged surface are observed in line with the preferential hydration of the ionic liquid anions. The findings are appropriately described using a two-level statistical model. The confinement effect on the structure and dynamics of the mixtures is thoroughly analyzed using the density and the potential of mean force profiles, as well as by the vibrational densities of the states of water molecules near the graphene surface. The orientation of water molecules and the water-induced structural transitions in the layer closest to the graphene surface are also discussed.